Serotonin-related functional genetic variants affect the occurrence of psychiatric and motor adverse events of dopaminergic treatment in Parkinson’s disease : a retrospective cohort study

Redenšek Trampuž, Sara (author), Blagus, Tanja (author), Trošt, Maja (author), Dolžan, Vita (author)

The serotonergic system is important in Parkinson’s disease (PD) pathogenesis as it can take over dopamine production after a large portion of dopaminergic neurons is lost through neurodegeneration. The aim of this study was to evaluate the effect of genetic variability of serotonergic genes on the occurrence of motor complications and psychiatric adverse events (AE) due to dopaminergic treatment. We enrolled 231 patients and their clinical data were collected. Genotyping was performed for eight genetic variants. Logistic regression was used for analysis. Carriers of the HTR1A rs6295 GC genotype (OR = 2.58; 95% CI = 1.15–5.78; p = 0.021), TPH2 rs4290270 AA genotype (OR = 2.78; 95% CI = 1.08–7.03; p = 0.034), and at least one TPH2 rs4570625 T allele (OR = 1.86; 95% CI = 1.00–3.44; p = 0.047) had increased risk for visual hallucinations (VH). Additionally, carriers of at least one SLC6A4 5-HTTPLR rs25531 S (OR = 0.52; 95% CI = 0.28–0.96; p = 0.037) or at least one L$_G$ allele (OR = 0.37; 95% CI = 0.14–0.97; p = 0.044) had a decreased chance for VH. Constructed haplotypes of the TPH2 showed increased risk for VH (OR = 1.94; 95% CI = 1.06–3.55; p = 0.032) and impulse control disorders (OR = 5.20; 95% CI = 1.86–14.50; p = 0.002). Finally, individual gene–gene interactions showed decreased odds for the development of motor AE. Our findings suggest that the serotonergic pathway may play an important role in the development of AE resulting from dopaminergic treatment.

• Language: English
• Keywords: Parkinson’s disease, motor complications, visual hallucinations, impulse control disorders, dyskinesia, polymorphism, serotonin, adverse event, pharmacogenomics
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2022
• Number of pages: 13 str.
• Numbering: Vol. 12, iss. 2, art. 266
• PID: 20.500.12556/RUL-137342
• UDC: 616.8
• ISSN on article: 2075-4426
• DOI: 10.3390/jpm12020266
• COBISS.SI-ID: 97247491
• Publication date in RUL: 13.06.2022

Record is a part of a journal

• Title: Journal of personalized medicine
• Shortened title: J. pers. med.
• Publisher: MDPI
• ISSN: 2075-4426
• COBISS.SI-ID: 31207641

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 11.02.2022

Secondary language

• Language: Slovenian
• Keywords: Parkinsonova bolezen, motorični zapleti, vizualne halucinacije

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P1-0170
• Name: Molekulski mehanizmi uravnavanja celičnih procesov v povezavi z nekaterimi boleznimi pri človeku

• Funder: ARRS - Slovenian Research Agency
• Project number: J7-2600
• Name: Presnovne možganske spremembe nevrodegenerativnih demenc in njihove korelacije s histopatološkimi spremembami v možganih